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SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium ( Cutibacterium ) acnes

Abstract : Overt infection by Propionibacterium acnes is lacking in many SAPHO syndromes, and antibiotics have only a transient and incomplete effect, either in SAPHO syndrome or acne. As several auto-inflammatory bone disorders sharing overproduction of IL-1β can mimic SAPHO, this syndrome could partly depend on genetically encoded overproduction of IL-1β. However, cyclic intracellular infections, mostly by P. acnes, can contribute to the enhanced IL-1β release by some skin cells, and probably by bone cells. P. acnes is indeed a powerful trigger of NLRP3-inflammasome activation and IL-1β, leading to osteitis and enhanced mesenchymal cells differentiation in osteoblasts. Recent advances in the understanding of acne suggest that first steps of this disorder are not driven by P. acnes, but by a relative deficiency of FoxO1 within the nucleus of sebaceous cells. A similar defect of FoXO1 in bone cells should also be sought in SAPHO, since repression of FoxO1 gene is found in lesional psoriasis skin, and is associated with an increased number of osteoblasts and high bone mass in mice. FoxO1 selectively promotes IL-1β production, so that its downregulation could help some P. acnes t escape innate immunity and persist in a latent state in bone cells, including mesenchymal stem cells. However, P. acnes itself possibly contributes to FoxO1 downregulation, like H. pylori infection which induces nuclear inactivation of FoxO1 in human gastric cells to slow down autophagic clearance. As bisphosphonates, which often improve SAPHO syndromes, enhance autophagy, it may be worth testing whether their combination with antibiotics is synergistic in SAPHO syndromes.
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Submitted on : Wednesday, June 13, 2018 - 11:46:36 AM
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Jean-Marie Berthelot, Stéphane Corvec, Gilles Hayem. SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium ( Cutibacterium ) acnes. Joint Bone Spine, Elsevier Masson, 2018, 85 (2), pp.171 - 176. ⟨10.1016/j.jbspin.2017.04.010⟩. ⟨inserm-01814460⟩



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